Synthesis of wound hormones



Patented Jan. 18, 1944 SYNTHESIS OF WOUND HORMONES James English, Jr., Hamden, Conn., and James Bonner and Arie J. Haagen-Smit, Pasadena, Calif., assignors to California Institute Research Foundation, Pasadena, Call! a comic--v ration of California No Drawing. Application November 30, 1940,- Serial No. 367,950

4 Claims.

Thisinvention relates to processes for the synthesis 01' certain wound hormones and to intermediates for use in such synthesis. Many plant tissue extracts are capable of inducing renewed growth activity in mature plant cells. These growth-inducing extracts are usually obtained from ground or heated tissues and they are capable of evoking cell division and cell enlargement in unwounded cells. Such active principles have been termed "wound hormones."

The present application is concerned more particularly with the synthetic production of 1- decene-1, IO-dicarboxylic acid, which substance has been found to be highly active in stimulating the process of healing wounds in plant tissue.

We have found that 1-decene-1,10-dicarboxylic acid may be synthesized by converting undecylenic acid or alkyl ester thereof to the half aldehyde of sebacic acid, or its alkyl ester, by treatment with a highly active oxidizing agent, such as ozone, for example. The oxidation product is then condensed with malonlc acid in the presence of an inert tertiary amine, such as pyridine, to give the corresponding 1,10-dicarboxy-decene-l, or l-carboxy-lO-carbalkoxydecene-l. If the ester group is present, it may be hydrolyzed off by heating in alkaline medium, and, after acidification, the desired acid is obtained. This series of reactions i outlined in the following fiow sheet in which the process is illustrated in term of methyl undecylenate:

In the examples given below a specific method of carrying out our invention is given. It isto be understood, however, that modifications may be made therein by those skilled in the art without departing from the spirit and scope of our invention.

Example I I Undecylenic acid methyl ester (B. P. 119-120 C., mm.) is ozonized in acetic acidsolution to the half aldehyde of methyl sebacate [B. P. 124-125 C. (4 mm.)l. 13 gins. of this product is mixed with 15 gms. of malonic acid and 15 gms. of drypyridine and heated under reflux for four hours. A vigorous evolution of carbon dioxide occurs in the early stages of the reaction.

The resulting clear solution is acidified, poured into water, and extracted with ether. After re- Example II Undecylenic acid ethyl ester is treated as in Example I. 1-carboxy-IO-carbmethoxy-decene-l is obtained as an intermediate. After alkaline hydrolysis and acidification, l-decene-1,10-dicarboxylic acid is obtained.

Example III Undecylenic acid butyl ester is treated as in Example I. 1-carboxy-10-carb-butoxy-decene-1 is obtained as an intermediate. AIter alkaline hydrolysis and acidification, 1-decene-1,10-dicarboxylic acid is obtained.

Example IV Undecylenic acid propyl ester is treated as in Example I. i-carboxy-IO-carbpropoxy-decene-l is obtained as an intermediate. Ai'ter alkaline hydrolysis and acidification, l-decene-LlO-dicarboxylic acid is obtained.

Exmnple V Undecylenic acid isopropyl ester is treated as v in Example I. l-carboxy-iO-carbisopropoxydecene-l is obtained as an intermediate. After alkaline hydrolysis and acidification, l-decene- Llo-dicarboxylic acid is obtained.

, Example VI Undecylenic acid is treated according to the process of Example I. l-decene-LlO-dicarboxylic acid is obtaineddirectly.

We claim: 1. In a process for the production of l-decene- 1.10-dicarboxylic acid, the steps comprising oxidizing a substance selected from the group consisting of undecylenic acid and alkyl esters thereof to form the half aldehyde of sebacic acid and alkyl esters thereof respectively, and condensing the oxidation product with malonic acid in the presence of an inert tertiary amine.

an alkyl ester of the half aldehyde of sebacic acid, condensing the oxidation product with malonic acid in the presence of an inert tertiary amine under heating, hydrolyzing the condensation product in alkaline medium, and recovering l-decene-1,10-dicarb0xylic acid.

4. In a process for the production of l-decene- 1,10-dicarboxylic acid, the steps comprising oxidizing a methyl ester of undecylenic acid with ozone to form the methyl ester of the half aldehyde of sebacic acid, condensing the oxidation product with malonic acid in the presence of pyridine, under heating, hydrolyzing the condensation product in alkaline medium, and recovering 1-decene-1,10-dicarboxyiic acid.

JAMES ENGLISH. JR.

JAMES BONNER.

ARIE J. HAAGEN-SMII'. 

